Molecular analysis of the role of streptococcal pyrogenic Exotoxin A (SPEA) in invasive soft-tissue infection resulting from Streptococcus pyogenes

Mol Microbiol. 1999 Aug;33(4):778-90. doi: 10.1046/j.1365-2958.1999.01525.x.


Epidemiological studies strongly implicate the bacterial superantigen, streptococcal pyrogenic exotoxin A (SPEA), in the pathogenesis of necrotizing soft-tissue infection and toxic shock syndrome resulting from Streptococcus pyogenes. SPEA can act as a superantigen and cellular toxin ex vivo, but its role during invasive streptococcal infection is unclear. We have disrupted the wild-type spea gene in an M1 streptococcal isolate. Supernatants from toxin-negative mutant bacteria demonstrated a 50% reduction in pro-mitogenic activity in HLA DQ-positive murine splenocyte culture, and up to 20% reduction in activity in human PBMC culture. Mutant and wild-type bacteria were then compared in mouse models of bacteraemia and streptococcal muscle infection. Disruption of spea was not associated with attenuation of virulence in either model. Indeed, a paradoxical increase in mutant strain-induced mortality was seen after intravenous infection. Intramuscular infection with the SPEA-negative mutant led to increased bacteraemia at 24 h and a reduction in neutrophils at the site of primary muscle infection. Purified SPEA led to a dose-dependent increase in peritoneal neutrophils 6 h after administration. SPEA is not a critical virulence factor in invasive soft-tissue infection or bacteraemia caused by S. pyogenes, and it could have a protective role in murine immunity to pyogenic infection. The role of this toxin may be different in hosts with augmented superantigen responsiveness.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Bacterial Proteins / analysis
  • Bacterial Proteins / genetics*
  • Bacterial Proteins / toxicity
  • Cells, Cultured
  • Disease Models, Animal
  • Exotoxins / analysis
  • Exotoxins / genetics*
  • Exotoxins / toxicity
  • Humans
  • Leukocyte Count
  • Membrane Proteins / analysis
  • Membrane Proteins / genetics*
  • Membrane Proteins / toxicity
  • Mice
  • Mutation
  • Neutrophils / immunology
  • Oligodeoxyribonucleotides
  • RNA, Messenger / metabolism
  • Staining and Labeling
  • Streptococcal Infections / immunology
  • Streptococcal Infections / microbiology*
  • Streptococcus pyogenes / genetics*
  • Streptococcus pyogenes / pathogenicity
  • Transformation, Bacterial
  • Virulence / genetics


  • Bacterial Proteins
  • Exotoxins
  • Membrane Proteins
  • Oligodeoxyribonucleotides
  • RNA, Messenger
  • SpeA protein, Streptococcus pyogenes